Mechanistic insights into the regulation of glucose‒lipid metabolism by the bioactive constituents of ginseng.

Panax ginseng Meyer (P. ginseng, PG), a historically used phytotherapeutic agent with a long history and wide-ranging applications, has garnered increasing attention in recent years because of its considerable pharmacological value. Amid the global rise in metabolic disorders, P. ginseng, as a natural product, has been demonstrated to contain various bioactive components-including ginsenosides, P. ginseng polysaccharides, and P. ginseng peptides-that have significant pharmacological effects on glucose and lipid metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). These bioactive compounds modulate glucose and lipid metabolism through multitarget mechanisms, including enhancing glucose uptake and glycogen synthesis, inhibiting gluconeogenesis, and regulating adipocyte differentiation and fatty acid oxidation, as well as through gut microbiota-mediated regulation of glucose‒lipid metabolism. These effects help alleviate pathological conditions such as insulin resistance (IR), inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, involving key signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor gamma (PPARγ). As a result, P. ginseng shows significant promise and holds great potential for preventing and treating glucose‒lipid metabolic disorders. Ongoing advances in research and technology may further elucidate its underlying mechanisms and facilitate clinical translation, paving the way for the development of more effective therapeutics for metabolic regulation.